Proteins encoded by the I region of the major histocompatibility region (Ia antigens) will be isolated from Ia-bearing tumor cells. The cells will be radiolabeled with 3H, 35S and/or 14C amino acids, detergent solubilized and isolated with immunoadsorbants, utilizing monoclonal anti-Ia alloantisera from hybridomas. Protocols for isolating cyanogen bromide and proteolytic fragments from both the alpha and beta chains of the Ia molecules labeled with a variety of 3H amino acids and 35S cys will be initially developed. These fragment isolation procedures will be designed to maximize the recoveries of the radiolabeled products. Once the peptide isolation procedures are established, Ia molecules will be uniformly radiolabeled with 14C, the peptides isolated and sequenced.